November 9, 2002

THERE are remarkable similarities across the numerous living species that inhabit our planet. This ubiquity owes itself to the nucleic acid molecules, especially Deoxyribonucleic acid (DNA).

The DNA is a molecule central to almost all life forms. DNA, with its famous double-helical structure, is the carrier of genetic information. The DNA hands over this genetic information to the messenger Ribonucleic Acids (mRNA’s). These mRNA’s, encode for various proteins. The manufacturing of proteins takes place in the special cellular machinery called ribosomes.

DNA is composed of two strands. Each strand of DNA has small repeated units called nucleotides. Each nucleotide is made up of one of four nitrogenous bases (adenosine, cytidine, thymidine and guanosine), a sugar (deoxyribose) and a phosphate group. Generally the nucleotide bases are represented as A, T, G or C. In the DNA strand this arrangement of the nucleotides is of crucial importance. A selected region of the DNA strand that is composed of a specific sequence of nucleotides, has the potential information to make a protein. This sequence is what we call a gene. Some proteins are formed from one gene only, whereas most of them require several genes. For example, the Hemoglobin protein, which carries oxygen in the blood, derives its structure from two proteins (alpha globin and beta globin). Different genes are needed for these alpha and beta globins.

The proteins are polymers of 20 different amino acids. Selecting from this set of available amino acids, many different combinations can be assembled — giving rise to an astounding variety of proteins The proteins can act in a whole variety of ways: whether as enzymes, bringing about and regulating the millions of chemical reactions in the humans or making up the structure of many organs and tissues.

DNA was identified as the hereditary material in 1944 and its structure was unraveled in 1953 by Watson and Crick, in a series of classic experiments. They shone X-rays on to DNA and what they saw was the famous double helix structure that marvelously adorns our textbooks today. The first gene was cloned in 1973 and the gene for insulin was separated in 1978.

Polymerase chain reaction (PCR) was discovered in 1983. DNA Polymerase is an enzyme that helps DNA reproduce itself or in other words, helps the molecule to replicate. DNA fingerprinting, a technique that could match the DNA extracted from two individuals was invented in 1984; and this opened doors for DNA-based forensic diagnosis (the art and science of investigating crimes) and geneopalaeontology (studying the evolution of species from genetic records trapped in fossils).

An inspiring milestone can be seen in this chronology. In 1968, Har Gobind Khorana (a graduate of the Punjab University) won the Nobel prize with his co-workers for breaking the code that translates DNA language into the protein language. The invention opened new vistas in genetic engineering.

Not surprisingly, all these resounding advances prompted the world’s leading scientists to think about the genetic make-up of humans themselves. They planned to uncover the mysteries of human genes to understand the nucleic origins of life, and to use this information for better health by diagnosing and treating diseases, developing drugs and retracing human history on the genetic ladder. The specialized laboratories in the field of genetic engineering around the globe started a world-wide effort to sequence all the human genes, that is, to locate the sequences of A, T, G, and C on all the DNA that is contained the human genome. This concerted effort was dubbed the Human Genome Project, one of the biggest scientific tasks ever undertaken worldwide. The Human Genome Project was formally lauched in 1990. Started by the US government, it was a 15-year project to be completed in 2005 at the cost of US$3 billion. It was almost completed in June 2000 and at a much lesser cost.

The HGP team’s technique was to chop the DNA into pieces and then find the sequence by matching patterns; but a rival private concern, Celera Genomics used a short-cut method, called “shot-gun sequencing”, because of which they were in a position to complete the project much earlier.

Later on there was a compromise and in June 2000 there was a joint statement by the HGP team and Celera Genomics announcing the completion of the Human Genome Project. So now the whole sequence of the 3.2 billion nucleotides is known, the Human Genome is complete, but this is just the first step.

To know what a particular gene does and how an alteration will affect life and possible remedies to the same is something that is far from completion today. This may require another twenty to thirty years and as time progresses and as the world’s researchers home in on genomic data, we may be entering an altogether new life and a new world called genomic era with other sister terms like proteomics for proteins, glycomics for carbohydrates and metabonomics for metabolites.

The human genome is all of the DNA material contained in a human cell, manifest in 23 pairs of chromosomes and 3.2 billion base pairs. Three per cent of the genomic DNA is occupied by about 100,000 genes. The 3 per cent of the genome (called the exonic portion) codes for the proteins. We do not yet completely know which genes code for which proteins, but the complete sequence of nucleotides is now an unfolded mystery - that is what it means when we say that the human genome has been mapped completely.

A very interesting fact that we come across is that all humans share about 99.9 percent of genome amongst themselves without appreciable differences. This astounding similarity belies the 7000 generations of human evolution — which is generally considered as the seed of genetic variation. We wonder if this isn’t an evidence enough to preach against racism and ethnic strife that has torn asunder the modern world. Man and chimpanzee have 97 per cent similarity and the figure stands at 75 per cent for the rat. Despite this correspondence, humankind appears to be remarkably different, in fact superior, to these species. The answer may lie in the non-coding 97 per cent of the genome. After all, this region may not be that barren at all. Probably the 3 per cent is only the tip of an iceberg! Only time and more concerted effort could help us reveal the complete secrets of the genome. Today by completing the genome, we have definitely found the key; what remains is finding the proper lock to open!

With the maturing of genetic technologies, it would also be possible to figure out genetic disorders — the simplest being a replacement of a single base (A, T, C or G) in the gene, for example, a T being replaced by G. These “Single Nucleotide Polymorphisms” or SNP’s are the markers of several serious malignancies like Huntington’s disease, cystic fibrosis, breast cancer, diabetes, phenylketonuria, Alzheimer’s and most important of all, coronary heart disease. If we know the genes, it would be possible to selectively replace the mutant genes with good ones by the excitingly developing methods of gene therapy.

Different companies are now using the publicly available sequences to come up with the medicines to rectify a particular genetic malfunction. A whole new area of genetic therapy has now dawned and taking its first few giant strides. These companies have done no sequencing themselves but can produce and market medicines that replace mutant genes with healthy ones. This would soon become a booming business worldwide.

With genetic therapy, personalized medication has now become a more viable possibility. Studies show that 10-40 per cent of all people receiving medical treatment respond less than perfectly to medication. Some drugs may work effectively on one patient but not the other — the answer lies once again, in delivering drugs that are gene-specific.

However, despite all these awe-inspiring wonders, many social and ethical issues remain. For example, insurance companies would like to know about genetic disorders in a person because if the person is predisposed to death within five years, they would be the least interested in providing insurance protection. If they were to offer insurance services to many of them, they could easily go bankrupt. Genetic information of an individual could be stored on a credit-card sized “National Genetic Card” that could be used and exploited by employers; the habits of criminals could be exposed and this could also be the mark of a new kind of genetic warfare.

Another area of major concern is that of patenting genetic information. Laws of nature cannot be granted a patent but genetically engineered vaccines and medication can. In 1995, for example, the HGP requested for a new patent on a gene that codes for a protein that helps the AIDS virus enter the victim cell. Granting patents would be a legally convoluted and difficult process in the first place.

Genetically modified crops, pesticides, transgenic animals and their meat — all pose social and moral challenges. The ultimate threat would appear when we would think of making human clones — with desired features. A scientifically aware and active society would always consider such questions before hand. The question we in Pakistan face is whether we are aware enough.

Changing the genome is a deep moral issue and our science alone does not equip us with sane decisions. At the end of the day, we must resort to our own collective consciousness and make the right decisions at the right time. As a nation, let us not wait for the bandwagon to cross by us and boogie behind its last carriage, let us instead, help steer it in the right direction.

Danyal Arif is Technical Support Engineer at Huawei Technologies in Islamabad. He has been a regular member of the Khwarzimic Science Society. Muhammad Sabieh Anwar, is a physics student at Oxford University and the joint secretary of the KSS www.khwarzimic.org 

Please Visit our Sponsor (Ads open in separate window)